Proteins serve an incredible variety of biological functions which are determined indirectly by the amino acid sequence in the protein. The most effective single method for sequence determination is the degradation technique of Edman, which is performed by an automated instrument manufactured by Beckman. By a repetitive sequence of processes, amino acids are chemically cleaved one by one from the N-terminal end of a large protein or polypeptide. Recently, proteins of considerable interest are being isolated only in minute quantities, too small for accurate determination on available automated instruments. The goal of our project is to discover improvements to the present protein sequencing methodology that will allow for "microsequencing." The present emphasis so far has been to make improvements in the design of the Beckman automated sequencer. The three main features in the design that have been improved are (1) reagent and solvent delivery valve mechanism, (2) vacuum system, (3) automatic conversion of cleaved amino acid to a more stable phenylthiohydantoin derivative for analysis. The modified Beckman sequencer is now being used to analyse proteins using 10 nmoles of sample with a repetitive yield of 95%. The next approach is to investigate other types of automated instrumentation for handling sub-nanomole quantities of proteins and peptides, for example, miniaturized solid-phase systems or membrane-based devices for Edman reaction and product separation. A prototype for a membrane-based sequencer has been constructed and will undergo preliminary testing.